Volume 33, Issue 2, Pages 137-138 (January 2009) BRCTing Up Is Hard to Do  David F. Stern  Molecular Cell  Volume 33, Issue 2, Pages 137-138 (January 2009) DOI: 10.1016/j.molcel.2009.01.005 Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 1 Assembly and Activation of Checkpoint Complexes Domains are not drawn to scale. For purposes of illustration, Rad53 FHA1 and FHA2 and SCD1 and SCD2 are used arbitrarily in these diagrams, but they do have separable functions. (A) Mec1-Ddc2 complex bound to ssDNA/RPA. Rad9 is a basal dimer/oligomer (broken red line), but actual contact sites are unmapped. DNA damage permits Rad9 Tudor to bind Met-histone (or damaged DNA) and BRCT to bind P-H2A (broken blue lines). (B) Mec1 (activated through Dpb11 and 9-1-1) phosphorylates colocalized Rad9 at SCD. Rad9-P-SCD binds to Rad9 BRCT. (C) Rad53 activation, phase I. Phosphorylated Rad9 recruits more Rad9 through BRCT and recruits Rad53 through FHA domains. Mec1 phosphorylates Rad53 SCD (red arrows). (D) Phase II. Concentration of Rad53 in Rad9 oligomers permits Rad53 crossphosphorylation at kinase and FHA domains (red arrows). Rad53 phosphorylates Rad9 BRCT, inhibiting interaction of BRCT with P-SCD (black arrow). (E) Rad53 phosphorylated by Mec1 or Rad53 recruits Dun1 through Dun1 FHA. (F) Phase III. Activation of new molecules of Rad53 and Dun1 in PIKK- and Rad9-independent complexes formed by FHA/P-SCD interactions. As discussed in the text, FHA phosphorylation may then promote dissociation. Molecular Cell 2009 33, 137-138DOI: (10.1016/j.molcel.2009.01.005) Copyright © 2009 Elsevier Inc. Terms and Conditions